Molecular Representations for AI in Chemistry and Materials Science: An NLP Perspective

Large Language Models (LLMs) are increasingly being used to support scientific discovery. In chemistry, tasks such as reaction prediction and structure elucidation require reasoning about the structures of molecules. As such, LLM-based systems for chemistry must interact reliably with molecular structures. Most previous studies of LLMs in chemistry have used SMILES strings or IUPAC names as molecular representations; however, the suitability of these formats has not been systematically assessed. In this work, we introduce MolJSON, a novel molecular representation for LLMs, and systematically compare it with five common chemical formats. We evaluated each representation with GPT-5-nano, GPT-5-mini, GPT-5, and Claude Haiku 4.5 using a set of 78,045 questions spanning translation, shortest path, and constrained generation reasoning tasks. We observed substantial variation across representations in the ability of LLMs to interpret and generate molecular graphs, with MolJSON consistently outperforming existing formats. On translation tasks, GPT-5 achieved 71.0% accuracy when converting IUPAC names to MolJSON, compared with 43.7% when converting the same inputs to SMILES. For constrained generation, GPT-5 reached 95.3% accuracy generating MolJSON, compared with 76.3% for IUPAC and 64.0% for SMILES. As an input format for shortest-path reasoning, GPT-5 successfully answered 98.5% of questions with MolJSON, compared with 92.2% for SMILES and 82.7% for IUPAC, whilst also using fewer reasoning tokens. We observed systematic errors associated with atom count and ring complexity for SMILES strings and IUPAC names, whereas MolJSON was more robust to these failure modes. Our results show that the choice of molecular representation has a material impact on LLM performance, and that explicit molecular graph schemas, such as MolJSON, are a promising direction for LLM-based systems in chemistry.

Large language models (LLMs) are increasingly used for molecular tasks, but it remains unclear which molecular representation to use. We present a systematic benchmark, MolRepBench, to evaluate LLM molecular competence across nine representations and eight chemical tasks. We benchmark 16 LLMs across five model families, including reasoning and non-reasoning variants, chemistry-specialized LLMs, and closed frontier models. Performance is strongly representation-dependent and no single representation wins across tasks, though CML is the best, followed by MolJSON, InChI and canonical SMILES. Explicit structured text representations (CML and MolJSON) dominate structural tasks; IUPAC dominates semantic tasks, winning molecule retrieval for all 16 LLMs; and SMILES variants are rarely optimal despite their prevalence in pretraining. Chemistry-specialized models perform well with SMILES at the cost of large degradations with structured text representations, suggesting SMILES-only evaluation rewards specialization that does not generalize. Using LLM-as-a- judge, we find that IUPAC produces the highest fraction of correct molecule generations. A mechanistic study via tokenization audits, linear probes, and attention shows that representations are encoded differently inside the model; for example, structured representations require more attention across the molecular span. Our results argue against representation-invariant evaluation and motivate task-aware representation routing for LLM-based chemistry.

The discovery and design of functional molecules remain central challenges across chemistry,biology, and materials science. While recent advances in machine learning have accelerated molecular property prediction and candidate generation, existing models tend to excel either in physical fidelity without transparent reasoning, or in flexible reasoning without guarantees of chemical validity. This imbalance limits the reliability of artificial intelligence systems in real scientific design workflows.Here we present Logos, a compact molecular reasoning model that integrates multi-step logical reasoning with strict chemical consistency. Logos is trained using a staged strategy that first exposes the model to explicit reasoning examples linking molecular descriptions to structural decisions, and then progressively aligns these reasoning patterns with molecular representations. In a final training phase, chemical rules and invariants are incorporated directly into the optimization objective, guiding the model toward chemically valid outputs. Across multiple benchmark datasets, Logos achieves strong performance in both structural accuracy and chemical validity, matching or surpassing substantially larger general-purpose language models while operating with a fraction of their parameters. Beyond benchmark evaluation, the model exhibits stable behaviour in molecular optimization tasks involving multiple, potentially conflicting constraints. By explicitly exposing intermediate reasoning steps, Logos enables human inspection and assessment of the design logic underlying each generated structure. These results indicate that jointly optimizing for reasoning structure and physical consistency offers a practical pathway toward reliable and interpretable AI systems for molecular science, supporting closer integration of artificial intelligence into scientific discovery processes.